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Autism Speaks Announces More than $1.2 Million in Fellowship Grants

September 24, 2008

Autism Speaks has announced a total of $1,244,000 in grants for seventeen new Pre-Doctoral and Post-Doctoral Fellowships – two-year grants awarded to support the efforts of graduate student and postdoctoral researchers working in fields related to autism. The fellowships will not only fund a diverse group of exciting research projects on the etiology, biology, diagnosis and treatment of autism, but, most importantly, will encourage the development of promising young scientists who wish to devote their careers to autism research.

Several recent studies having described abnormal brain connectivity in individuals with autism, and this year's fellowship group of applications increasingly focused on understanding the biological basis of these impairments. Defining the cellular and molecular mechanisms that underlie the changes in brain circuitry will be greatly facilitated by the identification of animal models with connectivity alterations that match those found in individuals with autism. One fellowship will be used to examine neural connectivity in a previously established genetic mouse model of autism. Focusing on the neural connections within the cortex, the fellow will examine whether the abnormal circuitry found in people with autism is replicated in these mice. If the project is successful, these data will define a strong new model system that researchers may use to examine how deficits in neural connectivity arise and are maintained, and to design new therapeutic strategies targeted at circuit modulation.

Abnormalities in neural connectivity in autism are likely to involve alterations in the development of synapses, the specialized points of contact between neurons that are responsible for transmitting information throughout the nervous system. Four fellows will be focusing on projects that attempt to draw a link between several specific genetic mutations found to be associated with autism and whether and how these mutations impact synaptic functioning. By doing so, these experiments may provide evidence that the diverse genes found to be mutated in autism functionally affect common cellular structures and pathways, which would support the overarching theory that neuronal connectivity is disrupted in autism. Most importantly, these projects may identify potential molecular targets for the design of novel pharmacological interventions.

As mentioned above, identifying gene variants associated with autism will help researchers understand the diverse molecular pathways and processes which contribute to autism. Towards this end, three grants were awarded to fellows who will use novel methodologies to uncover molecular and biochemical changes in populations of individuals with autism. Genetic mutations can affect the functional properties of a gene (for example, by causing the protein product of the gene to be inactive), but they can also affect how and where normally functioning genes are turned on and off. This is called gene expression, and some genetic mutations may cause genes to be expressed at abnormally high or low levels, or to be expressed in the wrong types of cells. In a project designed to examine the effects of this type of mutation, one fellow will compare the expression levels of thousands of genes in blood samples from individuals with autism to identify the genes that are expressed at abnormal levels in autism. A second fellow will be taking a much more focused approach by specifically examining blood levels of the enzyme methionine synthase, a metabolic protein that is extremely sensitive to environmental toxins, in order to explore the link between the environment, oxidative stress and metabolic function in autism. Finally, one fellow will examine the DNA of people with autism for novel, submicroscopic chromosomal rearrangements to illuminate new types of gene variation that confer autism risk. All of these exploratory investigations may lead to a better understanding of the molecular pathways affected in autism, as well as provide a basis for earlier and more precise diagnostic exams and recognition of subtypes of autism.

Five fellows will be utilizing the technique of Functional Magnetic Resonance Imaging (fMRI) to study patterns of brain activity in individuals with autism. These experiments will attempt to define the neural basis of several debilitating social impairments found in autistic patients, including why understanding the intentions and emotional states of others is so challenging, why attention-shifting in response to social cues is so difficult, and why many individuals with autism demonstrate problems adapting to new environments. Identification of the brain regions and neural networks responsible for these complex cognitive traits may provide the foundation for development of interventions to treat these aspects of social impairment. An additional project will utilize fMRI to focus on the very under-studied area of why individuals with autism show difficulties coordinating their motor response to sensory inputs (called “sensorimotor performance”).

Two fellows will be focusing their attention on the siblings of individuals with autism. Given their greater risk of developing autism due to a shared genetic and environmental background, one grant will study the younger siblings of children with autism to concentrate on atypical early development of cognitive and attentional processes, and whether there is a direct relationship with socialization skills. Another very innovative study will examine whether nonaffected siblings can be effective providers of a treatment intervention. Specifically, the fellow will study whether they can learn how to administer a naturalistic imitation intervention, and whether this will increase the social-communication skills of their affected siblings. Finally, in another novel method for improving treatment approaches a third fellow will study language acquisition in deaf children with autism. The visual aspect of learning American Sign Language (ASL) requires visual processing skills that may be impaired in autism, and identifying how and whether these impairments impact the acquisition of ASL will be useful in developing better teaching strategies for both deaf and hearing children with autism.